It has long been desired, in the treatment of different diseases, to be able specifically to deliver a pharmaceutical to a particular spot in the body, in particular in the treatment of tumours because of the grave systemic secondary effects produced by cytostatics. Various chemical methods have been tested in which it was tried to utilize differences in cell structure between tumour cells and healthy cells. However, no such test has been shown to give unequivocal results, above all because the difference between the tumour cells and the healthy cells is so insignificant.
One way of solving this problem is to utilize magnetic carriers of pharmaceuticals which are injected into the blood-vessel system and transported by the blood to be stopped at the target by means of a magnetic field.
U.S. Pat. No. 4,335,094 (priority June 2, 1977) discloses microspheres containing magnetic material incorporated with a polymer which, in addition, carries biologically active components.
U.S. Pat. No. 4,247,406 contains a detailed description of the use and production of magnetic microspheres made up of a magnetic material which has been enclosed in a polymer consisting of albumin.
One highly important reason for enclosing the magnetic material in a matrix, and for not using only the magnetic material, is that a matrix makes it possible to transport greater amounts of pharmalogically active substance per microsphere or microparticle, which is a prior condition of opening up possibilities of providing therapeutical concentrations of the pharmacologically active substances at the target site, without increasing the number of microspheres to such an extent that the capillaries are occluded. The requirements placed on the matrix used in such contexts are as follows:
1. The matrix should in itself be chemically inert in biological systems.
2. The matrix should be biologically well-characterised.
3. The matrix should be non-toxic and non-immunogenic.
4. The matrix should be dischargeable from the body via normal routes.
5. The matrix preparation should be readily administrable.
6. The matrix preparation should be able to release a biologically active substance, and the release rate of the active substance should be readily controllable.
7. The matrix should be usable for enclosing and releasing substances having different molecular weights.
In addition to polymers of amino acids, such as albumin, carbohydrates are conceivable. Starch and glycogen are such carbohydrates made up of glucose units and satisfying the requirements for biocompatibility, primarily because they are the body's own substances, which means that secondary effects in the form of hypersensitivity reactions are avoided. The body's own enzyme for degrading starch is alpha-amylase which specifically degrades alpha(1-4) bonds.
The use of starch is disclosed by DE-OS No. 25 24 278 which describes the preparation and utilization of covalent cross-linked microspheres of starch having a size so selected that the microspheres will get caught in the capillaries and thereby can be utilized as a diagnostic means in the vascular system. To ensure that these microspheres get caught, the size of the microsphere must be above 10 .mu.m.
To enable a microsphere injected into the vascular system to circulate, the diameter of the microsphere must be below 1 .mu.m. This has been shown by, inter alia, Okamoto et al (Chem. Pharm. Bull. (1975) 23(7), 1452-1457) who also have shown that the surface structure must be hydrophilic. The magnetic albumin microspheres previously mentioned are hydrophobic and cannot therefore circulate, but must be injected arterially towards the target site.
The present specification describes a simple and reproducible process for the production of magnetically responsive crystalline nanospheres or nanoparticles for the concentration of pharmaceuticals.